International team identifies bacteria which protect against type 1 diabetes.

To combat pathogens, the immune system has developed various mechanisms to detect, defend against and even destroy micro-organisms that are harmful to the body. This includes antimicrobial peptides and natural proteins that destroy pathogenic bacteria by disrupting their cellular membrane. Not only are they produced by immune cells, they are also produced by cells whose functions are not immune-related.

The human body has ten times the amount of microbes than it has human cells, this set of bacteria is called microbiota. In some instances, bacteria known as pathogens can cause infectious diseases. However, these micro-organisms can also protect a person from certain diseases. Now, an international team of researchers from Inserm, Paris Descartes University, Jiangnan University, Karolinska Institutet and the CNRS have recently shown how microbiota protects against the development of type 1 diabetes. The opensource study is published in the journal Immunity.

The team are currently focussing on a category of antimicrobial peptides, i.e. cathelicidins. Previous studies show that apart from their protective function, these peptides have also exhibited capabilities against several autoimmune diseases. As such, researchers hypothesise that cathelicidins may be involved in the control of type 1 diabetes, an autoimmune disease where certain cells in the immune system attack beta cells in the pancreas which secrete insulin.

The current study observed that beta pancreatic cells in non-diseased mice produce cathelicidins and that, interestingly, this production is impaired in diabetic mice. To test this hypothesis, the lab injected diabetic mice with cathelicidins where production is defective. Data findings show that injecting cathelicidins inhibits the development of pancreatic inflammation and, as such, suppresses the development of autoimmune disease in these mice.

Given that the production of cathelicidins is controlled by short-chain fatty acids produced by gut bacteria, the team are now studying the possibility that this may by the cause of the cathelicidin deficiency associated with diabetes. Indeed, results showed that diabetic mice have a lower level of short-chain fatty acids than that found in healthy mice. By transferring part of the gut bacteria from healthy mice to diabetic mice, the team re-established a normal level of cathelicidin. Meanwhile, the finding show that the transfer of micro-organisms reduces the occurrence of diabetes.

The lab surmise that this research is further evidence of the undeniable role microbiota plays in autoimmune diseases, particularly in controlling the development of autoimmune diabetes. They go on to conclude that preliminary data, as well as scientific literature, suggest that a similar mechanism may exist in humans, paving the way for new therapies against autoimmune diabetes.

Antimicrobial peptides (AMPs) expressed by epithelial and immune cells are largely described for the defense against invading microorganisms. Recently, their immunomodulatory functions have been highlighted in various contexts. However how AMPs expressed by non-immune cells might influence autoimmune responses in peripheral tissues, such as the pancreas, is unknown. Here, we found that insulin-secreting β-cells produced the cathelicidin related antimicrobial peptide (CRAMP) and that this production was defective in non-obese diabetic (NOD) mice. CRAMP administrated to prediabetic NOD mice induced regulatory immune cells in the pancreatic islets, dampening the incidence of autoimmune diabetes. Additional investigation revealed that the production of CRAMP by β-cells was controlled by short-chain fatty acids produced by the gut microbiota. Accordingly, gut microbiota manipulations in NOD mice modulated CRAMP production and inflammation in the pancreatic islets, revealing that the gut microbiota directly shape the pancreatic immune environment and autoimmune diabetes development. Pancreatic β-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota. Diana et al 2015.